Having a cotton swab probe into the deep recesses of your nose is hardly a pleasant experience, yet this minor form of torture has saved countless lives. Nasal swabs, and the polymerase chain reaction (PCR) tests used to analyze them, are one of the most effective methods to determine if people are carrying viruses, such as influenza-causing strains or the COVID-19-causing SARS-CoV-2 virus. Many public health experts agree that developing infrastructure to conduct diagnostic testing on an unprecedented global scale will be key in preventing future pandemics.
As scientists search for faster, cheaper, and more accurate means to conduct PCR tests and for other medical innovations to fight the spread of disease, the next breakthroughs might emerge from discoveries made in the most remote habitats on the planet—at the bottom of the ocean.
The Advent of Modern PCR
For something that can be so deadly, viruses are amazingly tiny, typically just tens of to a few hundred nanometers in diameter. They’re so tiny and contain so little genetic material that detecting them in a nasal swab would be an almost insurmountable challenge without assistance from PCR. PCR is a technique for duplicating genetic material, such as the single or double strands of DNA or RNA found inside viruses. With consecutive duplications, the quantity of genetic material increases exponentially until there is enough that it can be readily detected via routine laboratory techniques. (Duplicating genetic material from an RNA virus, such as the single-strand RNA in SARS-CoV-2, to allow detection involves initially converting the RNA into DNA via reverse transcription.)
Scientists figured out the fundamentals of duplicating DNA in the mid-1970s, but the process they were using was painfully slow. Duplicating DNA required temperatures up to 90°C (194°F), but at that temperature, the enzymes used to jump-start the process quickly broke down. After each round of duplication, the process thus had to be paused to add a new batch of enzymes. This stopping and starting took considerable time, so the hunt began for DNA-duplicating enzymes that remained stable at higher temperatures.
Custom enzymes can be created in the laboratory, but this process generally requires extensive testing, and there is no guarantee of success. As all living organisms contain their own DNA-duplicating enzymes, researchers suspected that nature might have already done the hard work of developing heat-tolerant enzymes. The key would be finding an organism that could survive at near-boiling temperatures. It turned out that two scientists, Thomas D. Brock and Hudson Freeze, had already found just such a critter in the hot springs of Yellowstone National Park.
Numerous species of extremophilic microbes—organisms that tolerate temperatures, salinities, acidity, or other conditions outside the habitable range of most species—thrive in the geothermally heated waters of Yellowstone. One of these species, discovered by Brock and Freeze in 1967 and named Thermus aquaticus, is particularly at home in almost-boiling waters and was later found to possess a thermally stable DNA-duplicating enzyme called Taq polymerase. By incorporating this enzyme into the PCR process, DNA duplication could be run continually and without pausing to add new enzymes. It was a watershed development for gene duplication and medical testing.
Yet the demands of modern PCR testing require that we improve this method further, for example, by using natural enzymes capable of withstanding even higher temperatures or replicating DNA with less potential for error (i.e., incorrectly replicated nucleotides).
The Promise of Deep-Sea Microbes
Thermus aquaticus and its enzymes are still central to modern PCR techniques, but this microbe is not the only species that can survive extreme temperatures. At the bottom of the ocean, there are fissures where hydrothermal vents spew jets of mineral-rich, superheated water at temperatures that can exceed 400°C (752°F)—that’s 4 times the boiling point of water at sea level. The only reason that this deep water does not immediately boil into a gas and evaporate is because of the crushing pressures at the bottom of the ocean.
Despite the combination of extreme temperatures and pressures, hydrothermal vents are surrounded by a bustling diversity of life that includes all-important, temperature-defying microbes. Inside one or more of these microbes could be the key to advances in PCR technology. In fact, useful molecules from species other than T. aquaticus have already been found: In 1991, scientists isolated another DNA-replicating enzyme, called Pfu polymerase, from the hydrothermal vent microbe Pyrococcus furiosus. Although Pfu polymerase is not as fast as Taq polymerase for replicating DNA, the resulting DNA contains far fewer errors, making it well suited for techniques that require high-fidelity DNA synthesis.
Deep-sea microbes from other environments may also hold secrets that could benefit medical or industrial applications, perhaps in unforeseeable ways. For example, in a recent study considering more than 50 species of microbes that live inside deep-sea sponges, researchers discovered that more than half the species contained chemicals that can serve as effective antibacterial or antifungal treatments. As the prevalence of antibiotic-resistant infectious pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), continues to grow worldwide, such new sources of antibiotics could be especially valuable if they can help circumvent these resistances.
These discoveries alone speak to the extraordinary value of deep-sea exploration, yet they represent only the tip of the iceberg. More than 90% of marine eukaryotes—and a far greater proportion of prokaryotes, including bacteria and archaea—have yet to be scientifically described. The vast array of naturally produced antibiotics that are still to be found in organisms living at the bottom of the ocean is therefore almost beyond imagining. Realizing medical benefits of these natural products, however, requires that we take the plunge and commit to exploring the dark, deep depths of the ocean. What we discover in these habitats could have wide-ranging implications that echo around the globe.
Exploring for Undiscovered Bounties
Despite the potential discoveries that await us at the bottom of the ocean, four fifths of this vast underwater realm remain unexplored and not mapped at high resolution. It is almost cliché, yet entirely true, to say that we have more accurate maps of the Moon’s surface than of the bottom of the ocean. As many people have pointed out, this disparity stems in part from chronic underfunding of deep-sea exploration, especially in comparison with space exploration. It is time to address this imbalance and promote deep-sea exploration at national and international levels.
A necessary first step in this exploration is to generate accurate and thorough maps of the entire seafloor. Such efforts have already begun, including the international Nippon Foundation-GEBCO (General Bathymetric Chart of the Oceans) Seabed 2030 Project, which aims to map 100% of the seafloor using modern sonar methods by 2030. With detailed maps of the structure of the entire seafloor, we can better identify those unique or particularly interesting habitats that could harbor bounties of undescribed species.
When we know where to focus our efforts, the next step is to explore these habitats firsthand, concentrating not only on the most charismatic of deep-sea species that often command our attention but also on tiny microbes that might otherwise go unnoticed. Indeed, as we have learned time and again—from the revelations of penicillin, Taq polymerase, and more—it is in the smallest organisms that sometimes the biggest discoveries are to be found.
This exploration will require submersibles, submarines, remotely operated vehicles, and other tools at the technological forefront of deep-sea exploration. The use of such high-tech equipment might sound expensive, but it is worth remembering that the cost of a single space shuttle launch in 2011, upward of $1 billion by some estimates, could have funded two deep-sea submersible dives per day for 110 years! So as we work to combat the ongoing COVID-19 pandemic and we think about what hazards the future could hold for our health, perhaps we need to spend a little less time looking at the stars and more time with our eyes under the water.
Nathan J. Robinson (firstname.lastname@example.org), Instituto de Ciencias del Mar, Consejo Superior de Investigaciones Científicas, Barcelona, Spain
Correction, 15 July 2022: This article has been updated to clarify that viruses can contain either single- or double-stranded DNA or RNA, and to remove a statement indicating that most viruses contain a single strand of DNA. Because there are likely many viruses that have not been identified, the most common type of viral genetic material is unknown. In addition, a statement was added to clarify that PCR, a DNA-duplicating technique, can be used to detect RNA viruses following the added step of reverse transcription.